Moderate-to-severe plaque-type psoriasis MedDRA version: 20.0 Level: LLT Classification code 10071117 Term: Plaque psoriasis System Organ Class: 100000004858
Conditions
Sponsors
UNION therapeutics A/S
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the Informed Consent Form (ICF) and in the protocol. 2. Male and female patients =18 years of age at the time of signing the ICF. 3. Body weight of >40 kg at the time of signing the ICF. 4. Diagnosis of chronic, stable plaque-type psoriasis at least 2 months before the Screening visit. If the patient is diagnosed with psoriasis arthritis, the arthritis should be stable. 5. Moderate-to-severe plaque-type psoriasis as defined by PASI =12, BSA =10%, and IGA =3 at the screening and baseline visits. 6. Candidate for systemic antipsoriatic treatment or phototherapy. 7. Women of childbearing potential (WOCBP) must have a negative serum pregnancy test at the Screening visit and a negative urine pregnancy test at the Baseline visit. In addition, sexually active WOCBP must agree to use a highly effective method of contraception until at least 4 weeks after the end of study treatment. Highly effective methods of contraception are those that have a failure rate of =65 years) yes F.1.3.1 Number of subjects for this age range 40
Exclusion criteria
Exclusion criteria: 1. Therapy-resistant psoriasis defined as =2 treatment failures due to inadequate efficacy within the past 5 years of any biologic therapies (including but not limited to etanercept, adalimumab, infliximab, certolizumab pegol, guselkumab, secukinumab, risankizumab, ixekizumab, tildrakizumab, or ustekinumab) administered in adequate dose and duration according to the label or local/national guidelines (patients who stopped systemic treatment for reasons not related to lack of efficacy are not excluded). 2. Unstable psoriasis or psoriatic arthritis (PsA) with acute deterioration within 4 weeks of the Screening visit. 3. History of allergy or hypersensitivity to any component of the study treatment. 4. Active infection (eg, bacteria, viral, fungal) requiring treatment with systemic antibiotics within 4 weeks of the Screening visit. 5. Malignancy or history of malignancy except for treated (ie, cured) basal cell skin carcinomas. 6. Current diagnosis of predominant guttate, erythrodermic, exfoliative, or pustular psoriasis, or of drug-induced psoriasis, or other skin conditions that might confound the evaluation of psoriasis vulgaris, as judged by the Investigator (eg, atopic dermatitis, lupus). 7. Any recurrent medical condition associated with serious gastrointestinal diseases, such as inflammatory bowel disease. 8. Any medical or psychiatric condition (eg, current major depression with a score for depressive symptoms =15 of Hospital Anxiety and Depression Scale at Baseline, schizophrenia, suicidal behavior, psychiatric hospitalization within the prior year) which, in the Investigator's opinion, would preclude the patient from adhering to the protocol, completing the study per protocol, and/or would place the patient at unacceptable risk for receiving the investigational therapy. 9. Any therapies and systemic treatments as described in Table 3 of Clinical Study Protocol which do not comply with the indicated washout interval. 10. Any previous treatment with orismilast or failure of treatment with apremilast or any other systemic phosphodiesterase-4 (PDE4) inhibitor as described in Table 3 of Clinical Study Protocol. 11. Any condition, including laboratory or ECG abnormalities, that places the patient at unacceptable risk to participate in the study or confounds the ability to interpret data from the study. 12. Severe hepatic impairment based upon medical history and laboratory abnormalities (eg, low albumin and abnormal bilirubin). 13. Any of the following abnormalities in clinical laboratory tests at Screening, as assessed by the study-specific laboratory and confirmed by a single repeat, if deemed necessary: a. Absolute neutrophil count of 1.5 × the upper limit of normal (ULN); patients with a history of Gilbert's syndrome may have a direct bilirubin measured and would be eligible for this study provided the direct bilirubin is =ULN; f. Alanine aminotransferase or aspartate aminotransferase >2.5 × the ULN; g. Serum creatinine =1.5 mg/dL. For a patient with a value of =1.5 mg/dL, a creatinine clearance of =60 mL/min (calculated using the CKDEPI Creatinine Equation) is allowed. 14. History or evidence of hepatitis B virus (HBV) infection at Screening. Patients with positive hepatitis B surface antigen (HBsAg) are exclu
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to evaluate the efficacy and safety of a modified-release orismilast tablet versus placebo in adults with moderate-to-severe plaque-type psoriasis.;Secondary Objective: Evaluate the dose response of orismilast and identify the dose with the best benefit/risk ratio to be evaluated in a Phase 3 program.;Primary end point(s): The primary endpoint in this study is the percentage change in Psoriasis Activity and Severity Index (PASI) score from Baseline at Week 16.;Timepoint(s) of evaluation of this end point: As specified in the endpoints. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Key Secondary Endpoints: • Patients achieving 75% reduction in PASI (PASI75) response at Week 16. • Patients achieving a score of Clear (0) or Almost Clear (1) and an at least 2-point improvement in Investigator Global Assessment (IGA) at Week 16. Other Secondary Endpoints: • Patients achieving a score of Clear (0) or Almost Clear (1) and an at least 2-point improvement in IGA at Weeks 4, 8, 12, and 20. • Patients achieving PASI75 response at Weeks 4, 8, 12, and 20. • Patients achieving 50% reduction in PASI (PASI50) and 90% reduction in PASI (PASI90) response at Weeks 4, 8, 12, 16, and 20. • Change from Baseline in PASI at Weeks 4, 8, 12, and 20. • Change from Baseline in total Psoriasis Symptoms Scale (PSS) score at Weeks 4, 8, 12, 16, and 20. • Change from Baseline in each individual item of the PSS at Weeks 4, 8, 12, 16, and 20. • Change from Baseline in the affected body surface area (BSA) at Weeks 4, 8, 12, 16, and 20. • Change from Baseline in Dermatology Life Quality Index (DLQI) score at Weeks 16 and 20. • Patients experiencing psoriasis rebound by Week 20, defined as PASI =125% of Baseline or new generalized pustular, erythrodermic, or more inflammatory psoriasis.;Timepoint(s) of evaluation of this end point: As specified in the endpoints. | — |
Countries
Germany, Poland, United Kingdom, United States
Contacts
Public ContactCharlotte Oersted Pedersen
UNION therapeutics A/S
Outcome results
None listed